title: The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe.
abstract: The chemokine receptor CCR5 is encoded by the CMKBR5 gene located on the p21.3 region of human chromosome 3, and constitutes the major co-receptor for the macrophage-tropic strains of HIV-1. A mutant allele of the CCR5 gene, Delta ccr5 , was shown to provide to homozygotes with a strong resistance against infection by HIV. The frequency of the Delta ccr5 allele was investigated in 18 European populations. A North to South gradient was found, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%). Highly polymorphic microsatellites (IRI3.1, D3S4579 and IRI3.2, D3S4580 ) located respectively 11 kb upstream and 68 kb downstream of the CCR5 gene deletion were used to determine the haplotype of the chromosomes carrying the Delta ccr5 variant. A strong linkage disequilibrium was found between Delta ccr5 and specific alleles of the IRI3.1 and IRI3.2 microsatellites: >95% of the Delta ccr5 chromosomes carried the IRI3.1-0 allele, while 88% carried the IRI3.2-0 allele. These alleles were found respectively in only 2 or 1.5% of the chromosomes carrying a wild-type CCR5 gene. From these data, it was inferred that most, if not all Delta ccr5 alleles originate from a single mutation event, and that this mutation event probably took place a few thousand years ago in Northeastern Europe. The high frequency of the Delta ccr5 allele in Caucasian populations cannot be explained easily by random genetic drift, suggesting that a selection advantage is or has been associated with homo- or heterozygous carriers of the Delta ccr5 allele.
authors.affiliation: IRIBHN and Service de Génétique Médicale, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium.
authors.forename: F
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authors.lastname: Libert
authors.forename: P
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authors.lastname: Cochaux
authors.forename: G
authors.initials: G
authors.lastname: Beckman
authors.forename: M
authors.initials: M
authors.lastname: Samson
authors.forename: M
authors.initials: M
authors.lastname: Aksenova
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authors.lastname: Cao
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authors.lastname: Czeizel
authors.forename: M
authors.initials: M
authors.lastname: Claustres
authors.forename: C
authors.initials: C
authors.lastname: de la Rúa
authors.forename: M
authors.initials: M
authors.lastname: Ferrari
authors.forename: C
authors.initials: C
authors.lastname: Ferrec
authors.forename: G
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authors.lastname: Glover
authors.forename: B
authors.initials: B
authors.lastname: Grinde
authors.forename: S
authors.initials: S
authors.lastname: Güran
authors.forename: V
authors.initials: V
authors.lastname: Kucinskas
authors.forename: J
authors.initials: J
authors.lastname: Lavinha
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: G
authors.initials: G
authors.lastname: Ogur
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
authors.forename: C
authors.initials: C
authors.lastname: Rosatelli
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: V
authors.initials: V
authors.lastname: Spitsyn
authors.forename: L
authors.initials: L
authors.lastname: Timar
authors.forename: L
authors.initials: L
authors.lastname: Beckman
authors.forename: M
authors.initials: M
authors.lastname: Parmentier
authors.forename: G
authors.initials: G
authors.lastname: Vassart
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D000483:Alleles; D018900:Dinucleotide Repeats; D005060:Europe; D005061:Europe, Eastern / Q000208:ethnology; D017353:Gene Deletion; D005787:Gene Frequency; D005819:Genetic Markers; D015497:HIV-1 / Q000276:immunology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D019713:Receptors, CCR5